Factors that provide translational control by inhibiting peptide initiation will be isolated and characterized in rabbit reticulocytes and Friend leukemia cells. Hemin deficiency and double-straned RNA will be used to induce inhibitors in reticulocytes. Inhibitors will be induced with interferon and double-stranded RNA in Friend leukemia cells. A comparison of the physical properties and mechanism by which the inhibitors block peptide initiation will be made and they will be compared with two distinct types of inhibitors that were isolated previously from different lines of Friend leukemia cells. One of these inhibitors appears to be a cAMP-independent protein kinase for the smallest subunit of the peptide initiation factor, eIF-2. The other appears to block mRNA binding and not to function as a protein kinase. Emphasis will be placed on the mechanism by which the inhibitors of peptide initiation are activated under various conditions, including during induced differentiation in Friend leukemia cells. The ultimate objective is to establish conditions by which these inhibitory systems can be selectively activated in vivo in transformed cells.